Previous studies in LID suggested that the low virulence of rotaviruses isolated from undergoing asymptomatic infection in a newborn nursery in which this virus was endemic was determined primarily by the VP4 gene of these strains. This interpretation was based on (i) the high degree of sequence relatedness of the VP4 gene of the M37 strain (originally derived from an asymptomatic newborn baby in Venezuela) with the corresponding gene of other strains recovered in diverse geographic locations from infants who underwent asymptomatic infection in newborn nurseries in which rotavirus was endemic, and (ii) the distinctness of the aforementioned VP4 genes from those present in strains isolated from older infants who had diarrheal disease. To determine whether or not this was a consistent finding, we obtained additional specimens from (i) infants who underwent a silent infection in a nursery in which rotavirus was endemic or (ii) infants who had a sporadic asymptomatic infection in a setting in which rotavirus was not endemic. These specimens collected from diverse geographic locations were examined by a dot hybridization assay or partial sequence analysis of the VP4 gene. Our observations suggest that the M37 VP4 gene allele (now designated as VP4 serotype 2) is associated with persistent transmission of asymptomatic rotavirus infection in newborn nurseries. However, host factors also play a role in sporadic asymptomatic neonatal infection that occurs in nurseries in which rotavirus is not endemic.